Cai Chenghan, Choy Jenny S, He Ge, Widlansky Michael E, Kassab Ghassan S, Fan Lei
Department of Mechanical Engineering, Michigan State University, Michigan, MI, USA.
California Medical Innovations Institute, San Diego, CA, USA.
Comput Biol Med. 2025 Oct;197(Pt B):111113. doi: 10.1016/j.compbiomed.2025.111113. Epub 2025 Sep 20.
Pulmonary hypertension (PH), defined by elevated mean pulmonary arterial pressure (mPAP), is a leading cause of right heart failure (RHF). However, the mechanisms linking PH to ventricular dysfunction and coronary ischemia remain unclear. An advanced mechanistic understanding is critical for improving clinical diagnosis and treatment strategies. This study aimed to investigate the impact of acute and chronic PH on biventricular mechanics and coronary perfusion. We developed a computational model that integrates coronary perfusion in the major coronary arteries with a biventricular finite element (FE) model in a closed-loop systemic and pulmonary circulation. Validated against clinical measurements, the computational model was applied to simulate the hemodynamics and myocardial perfusion across coronary territories and myocardial walls under conditions of acute and chronic PH. Model predictions demonstrated that in acute PH, coronary flow in the right ventricular free wall (RVFW) and septum was reduced due to elevated intramyocardial pressure (IMP), especially in the endocardium. In chronic PH, coronary flow was reduced in the RVFW, septum, and left ventricular free wall (LVFW) due to diminished perfusion pressure. These findings are consistent with clinical observations: the right-dominant right coronary artery (RCA) is more vulnerable to ischemia in acute PH, whereas the left-dominant left circumflex artery (LCx) is more vulnerable in chronic PH. In conclusion, chronic PH may contribute to subclinical left ventricular dysfunction and increased ischemic risk through impaired coronary perfusion, highlighting potential targets for therapeutic interventions in PH-related RHF.
肺动脉高压（PH），定义为平均肺动脉压（mPAP）升高，是右心衰竭（RHF）的主要原因。然而，将PH与心室功能障碍和冠状动脉缺血联系起来的机制仍不清楚。深入的机制理解对于改善临床诊断和治疗策略至关重要。本研究旨在探讨急性和慢性PH对双心室力学和冠状动脉灌注的影响。我们开发了一个计算模型，该模型将主要冠状动脉的冠状动脉灌注与闭环体循环和肺循环中的双心室有限元（FE）模型相结合。该计算模型经过临床测量验证后，被应用于模拟急性和慢性PH条件下冠状动脉区域和心肌壁的血流动力学和心肌灌注。模型预测表明，在急性PH中，右心室游离壁（RVFW）和室间隔的冠状动脉血流因心肌内压（IMP）升高而减少，尤其是在心内膜。在慢性PH中，由于灌注压力降低，RVFW、室间隔和左心室游离壁（LVFW）的冠状动脉血流减少。这些发现与临床观察结果一致：在急性PH中，右优势的右冠状动脉（RCA）更容易发生缺血，而在慢性PH中，左优势的左旋支动脉（LCx）更容易发生缺血。总之，慢性PH可能通过损害冠状动脉灌注导致亚临床左心室功能障碍和缺血风险增加，突出了PH相关RHF治疗干预的潜在靶点。
